Characterizing the Acute Phase Response in Healthy Patients Following Total Joint Arthroplasty: Predictable and Consistent

Abstract

Background: During surgery, trauma to musculoskeletal tissue induces a systemic reaction known as the acute phase response (APR). When excessive or prolonged, the APR has been implicated as an underlying cause of surgical complications. The purpose of this study was to determine the typical APR following total joint arthroplasty in a healthy population defined by the Charlson Comorbidity Index (CCI).

Methods: This retrospective study identified 180 healthy patients (CCI < 2) who underwent total joint arthroplasty by a single surgeon for primary osteoarthritis from 2013 to 2015. Serial measurements of C-reactive protein (CRP) and fibrinogen were obtained preoperative, perioperative, and at 2 and 6 weeks postoperative.

Results: Postoperative CRP peaked during the inpatient period and returned to baseline by 2 weeks. Fibrinogen peaked after CRP and returned to baseline by 6 weeks. Elevated preoperative CRP correlated with a more robust postoperative APR for both total hip arthroplasty and total knee arthroplasty, suggesting that a patient's preoperative inflammatory state correlates with the magnitude of the postoperative APR.

Conclusion: Measurement of preoperative acute phase reactants may provide an objective means to predict a patient's risk of postoperative dysregulation of the APR and complications.

Keywords: C-reactive protein; acute phase response; fibrinogen; healthy; total joint arthroplasty.

Fig. 1.

The perioperative rise and fall of 2 acute phase markers. (A) Mean circulating levels of CRP and FBG in response to TKA and THA in the study populations. Y-error bars depict a CI of 95%, and asterisks indicate significant difference between cohorts. (B) Unpaired t tests were performed to compare groups. Statistical significance denoted by * and defined as P < .05. CRP, C-reactive protein; FBG, fibrinogen; TKA, total knee arthroplasty; THA, total hip arthroplasty; CI, confidence interval; SD, standard deviation.

Fig. 2.

The influence of preoperative CRP on the rise and fall of mean fibrinogen following THA. Cohorts defined by the 25th or 75th percentile of preoperative CRP. Y-error bars depict a CI of 95%, and * indicates significant difference between the 25th and 75th percentile. Unpaired t tests were performed to compare groups. Statistical significance denoted by * and defined as P < .05.

Fig. 3.

The influence of preoperative CRP on the rise and fall of mean fibrinogen following TKA. Cohorts defined by the 25th or 75th percentile of preoperative CRP. Y-error bars depict a CI of 95%, and * indicates significant difference between the 25th and 75th percentile. Unpaired t tests were performed to compare groups. Statistical significance denoted by * and defined as P < .05.

Fig. 4.

The acute phase response (APR) and Virchow’s triad following total joint arthroplasty. (A) Damage induced by surgery initiates the acute phase response, a necessary component of wound healing. An unresolved acute phase response can result in chronic inflammation which further elevates acute phase reactants. While the APR is necessary for tissue regeneration, the lack of resolution can lead to life-threatening coagulopathies and poor wound healing. (B) The intersection of the Virchow’s triad and the acute phase response. CRP, a short half-life acute phase reactant, peaks close to the time of injury. As such, CRP is highly associated with injury. Fibrinogen, a long half-life acute phase reactant, is an integral factor in hemostasis and can lead to hypercoagulable states if elevated. Thus, CRP and fibrinogen are directly related to 2 components of Virchow’s triad: tissue injury and hypercoagulability.